Cheek support affects lung mechanics measurements of tidal-based spontaneous breathing.

BACKGROUND AND OBJECTIVE: Patients are required to support their cheeks during breath-occluding lung function tests. This prevents cheek expansion which would alter pressure measured at the mouth, and, consequently, lung mechanics measurements. To date, the effect of cheek support on airway resistance measurements has been assessed. However other lung mechanics have not been studied as thoroughly, and no algorithm to account for the effect of missing cheek support on lung mechanics measurements has been developed. METHODS: Lung mechanics were assessed with a breath occlusion test during light panting in healthy subjects with and without cheek support in a body plethysmograph. Average model-based airway resistance, lung elastance, and a parameter representing the viscoelastic were measured. Results were compared to quantify the effect of cheek support on these three parameters. RESULTS: In the nine healthy subjects (5 Female, 4 Male) recruited for this study, all mechanics tended to be underestimated when cheeks were unsupported. Changes in elastance, resistance, and viscoelastic parameter ranged between 1.6-66.8 %, -4.5-21.8 %, and -4.7-68.2 %, respectively, when cheek support was added. The underestimation was due to reduced mouth pressure during cheek expansion when the breath was occluded. The variance of lung mechanics parameters did not change with cheek support in all subjects. CONCLUSIONS: The error in lung mechanics measurement caused by unsupported cheeks was subject dependent. Hence, no rule-of-thumb could be identified to reconstruct missing cheek support. For correct lung mechanics measurements during breath-occluding lung tests, patients must have adequate cheek support. ABBREVIATIONS: ROCC: Occlusion resistance; COPD: Chronic Obstructive Pulmonary Disorder; SB: spontaneous breathing.

Variation of the maximum velocity along the umbilical vein supports the Reynolds pulsometer model.

OBJECTIVE: To challenge, with a modern sonographic approach and a numerical model, the Reynolds's concept which suggests that the vascular structure of the umbilical cord could act as a pulsometer facilitating the venous return to the foetus. METHOD: Forty-five patients between 20 and 28 weeks of gestation were included in the study. The blood maximum velocity in the umbilical vein, measured at both foetal and placental ends, was assessed. Several sonographic parameters of the cord, including the diameter of the umbilical vein at both extremities, cord cross-sectional area and Wharton's jelly section surface were measured. We compare our data with those of a numerical model. RESULTS: A difference in maximum velocity between the two extremities of the umbilical vein (ΔUVVmax) was noted. The maximum velocity was significantly higher at the foetal umbilical end (14.12 +/-3.18 cm/s) than at the placental end (11.93 +/-2.55 cm/s; p < 0.0001). The mean difference is 2.2 +/- 2.3 cm/s. No difference in the umbilical vein diameter was measured at both cord ends (umbilical 4.85 +/-0.9 mm, placental 4.86 +/-0.87 mm, p < 0.0001). There is no significant relationship between ΔUVVmax and the cord cross-sectional area or Wharton's jelly index. CONCLUSION: Modifications of the spatial velocity profile together with the pulsometer model could explain the maximum velocity changes that is measured in the umbilical vein along the cord. This numerical model consolidates the sonographic observations.

Inspiratory respiratory mechanics estimation by using expiratory data for reverse-triggered breathing cycles.

BACKGROUND AND OBJECTIVE: Model-based lung mechanics monitoring can provide clinically useful information for guiding mechanical ventilator treatment in intensive care. However, many methods of measuring lung mechanics are not appropriate for both fully and partially sedated patients, and are unable provide lung mechanics metrics in real-time. This study proposes a novel method of using lung mechanics identified during passive expiration to estimate inspiratory lung mechanics for spontaneously breathing patients. METHODS: Relationships between inspiratory and expiratory modeled lung mechanics were identified from clinical data from 4 fully sedated patients. The validity of these relationships were assessed using data from a further 4 spontaneously breathing patients. RESULTS: For the fully sedated patients, a linear relationship was identified between inspiratory and expiratory elastance, with slope 1.04 and intercept 1.66. The r value of this correlation was 0.94. No cohort-wide relationship was determined for airway resistance. Expiratory elastance measurements in spontaneously breathing patients were able to produce reasonable estimates of inspiratory elastance after adjusting for the identified difference between them. CONCLUSIONS: This study shows that when conventional methods fail, typically ignored expiratory data may be able to provide clinicians with the information needed about patient condition to guide MV therapy.

A virtual patient model for mechanical ventilation.

BACKGROUND AND OBJECTIVES: Mechanical ventilation (MV) is a primary therapy for patients with acute respiratory failure. However, poorly selected ventilator settings can cause further lung damage due to heterogeneity of healthy and damaged alveoli. Varying positive-end-expiratory-pressure (PEEP) to a point of minimum elastance is a lung protective ventilator strategy. However, even low levels of PEEP can lead to ventilator induced lung injury for individuals with highly inflamed pulmonary tissue. Hence, models that could accurately predict peak inspiratory pressures after changes to PEEP could improve clinician confidence in attempting potentially beneficial treatment strategies. METHODS: This study develops and validates a physiologically relevant respiratory model that captures elastance and resistance via basis functions within a well-validated single compartment lung model. The model can be personalised using information available at a low PEEP to predict lung mechanics at a higher PEEP. Proof of concept validation is undertaken with data from four patients and eight recruitment manoeuvre arms. RESULTS: Results show low error when predicting upwards over the clinically relevant pressure range, with the model able to predict peak inspiratory pressure with less than 10% error over 90% of the range of PEEP changes up to 12 cmH2O. CONCLUSIONS: The results provide an in-silico model-based means of predicting clinically relevant responses to changes in MV therapy, which is the foundation of a first virtual patient for MV.

A comparison between four techniques to measure cardiac output.

Cardiac output is an important variable when monitoring hemodynamic status. In particular, changes in cardiac output represent the goal of several circulatory management therapies. Unfortunately, cardiac output is very difficult to estimate, either in experimental or clinical settings. The goal of this work is to compare four techniques to measure cardiac output: pressure-volume catheter, aortic flow probe, thermodilution, and the PiCCO monitor. These four techniques were simultaneously used during experiments of fluid and endotoxin administration on 7 pigs. Findings show that, first, each individual technique is precise, with a relative coefficient of repeatability lower than 7 %. Second, 1 cardiac output estimate provided by any technique relates poorly to the estimates from the other 3, even if there is only small bias between the techniques. Third, changes in cardiac output detected by one technique are only detected by the others in 62 to 100 % of cases. This study confirms the difficulty of obtaining a reliable clinical cardiac output measurement. Therefore, several measurements using different techniques should be performed, if possible, and all such should be treated with caution.

Importance of metabolism variations in a model of extracorporeal carbon dioxide removal.

Extracorporeal CO2 Removal device is used in clinics when a patient suffers from a pulmonary insufficiency like Acute Respiratory Distress Syndrome and allows to decarboxylate blood externally. In this work, a model of the respiratory system coupled with such a device is proposed to analyze the decrease of CO2 partial pressure in blood. To validate the model, some parameters are estimated thanks to experimental data. Metabolism is a crucial parameter and we show that its time evolution must be taken into account in order to have correct CO2 partial pressure simulations in arteries and in veins.

Veno-venous extracorporeal CO2 removal improves pulmonary hemodynamics in a porcine ARDS model.

BACKGROUND: Protective lung ventilation is recommended in patients with acute respiratory distress syndrome (ARDS) to minimize additional injuries to the lung. However, hypercapnic acidosis resulting from ventilation at lower tidal volume enhances pulmonary hypertension and might induce right ventricular (RV) failure. We investigated if extracorporeal veno-venous CO2 removal therapy could have beneficial effects on pulmonary circulation and RV function. METHODS: This study was performed on an experimental model of ARDS obtained in eight anaesthetized pigs connected to a volume-cycled ventilator. A micromanometer-tipped catheter was inserted into the main pulmonary artery and an admittance micromanometer-tipped catheter was inserted into the right ventricle. RV-arterial coupling was derived from RV pressure-volume loops. ARDS was obtained by repeated bronchoalveolar lavage. Protective ventilation was then achieved, and the pigs were connected to a pump-driven extracorporeal membrane oxygenator (PALP, Maquet, Germany) in order to achieve CO2 removal. RESULTS: ARDS induced severe hypercapnic acidosis. Systolic pulmonary artery pressure significantly increased from 29.6±1.8 to 43.9±2.0 mmHg (P<0.001). After the PALP was started, acidosis was corrected and normocarbia was maintained despite protective ventilation. Pulmonary artery pressure significantly decreased to 31.6±3.2 mmHg (P<0.001) and RV-arterial coupling significantly improved (RV-arterial coupling index=1.03±0.33 vs. 0.55±0.41, P<0.05). CONCLUSION: Veno-venous CO2 removal therapy enabled protective ventilation while maintaining normocarbia during ARDS. CO2 removal decreased pulmonary hypertension and improved RV function. This technique may be an effective lung- and RV-protective adjunct to mechanical ventilation.

Stroke Volume estimation using aortic pressure measurements and aortic cross sectional area: Proof of concept.

Accurate Stroke Volume (SV) monitoring is essential for patient with cardiovascular dysfunction patients. However, direct SV measurements are not clinically feasible due to the highly invasive nature of measurement devices. Current devices for indirect monitoring of SV are shown to be inaccurate during sudden hemodynamic changes. This paper presents a novel SV estimation using readily available aortic pressure measurements and aortic cross sectional area, using data from a porcine experiment where medical interventions such as fluid replacement, dobutamine infusions, and recruitment maneuvers induced SV changes in a pig with circulatory shock. Measurement of left ventricular volume, proximal aortic pressure, and descending aortic pressure waveforms were made simultaneously during the experiment. From measured data, proximal aortic pressure was separated into reservoir and excess pressures. Beat-to-beat aortic characteristic impedance values were calculated using both aortic pressure measurements and an estimate of the aortic cross sectional area. SV was estimated using the calculated aortic characteristic impedance and excess component of the proximal aorta. The median difference between directly measured SV and estimated SV was -1.4ml with 95% limit of agreement +/- 6.6ml. This method demonstrates that SV can be accurately captured beat-to-beat during sudden changes in hemodynamic state. This novel SV estimation could enable improved cardiac and circulatory treatment in the critical care environment by titrating treatment to the effect on SV.

A simplified model for mitral valve dynamics.

Located between the left atrium and the left ventricle, the mitral valve controls flow between these two cardiac chambers. Mitral valve dysfunction is a major cause of cardiac dysfunction and its dynamics are little known. A simple non-linear rotational spring model is developed and implemented to capture the dynamics of the mitral valve. A measured pressure difference curve was used as the input into the model, which represents an applied torque to the anatomical valve chords. A range of mechanical model hysteresis states were investigated to find a model that best matches reported animal data of chord movement during a heartbeat. The study is limited by the use of one dataset found in the literature due to the highly invasive nature of getting this data. However, results clearly highlight fundamental physiological issues, such as the damping and chord stiffness changing within one cardiac cycle, that would be directly represented in any mitral valve model and affect behaviour in dysfunction. Very good correlation was achieved between modeled and experimental valve angle with 1-10% absolute error in the best case, indicating good promise for future simulation of cardiac valvular dysfunction, such as mitral regurgitation or stenosis. In particular, the model provides a pathway to capturing these dysfunctions in terms of modeled stiffness or elastance that can be directly related to anatomical, structural defects and dysfunction.

[One-dimensional time-dependent model of the cardiac pacemaker activity induced by the mechanoelectric feedback in a thermo-electro-mechanical background]. / Modèle unidimensionnel instationnaire de l'activité pacemaker cardiaque induite par le feedback mécano-électrique dans un environnement thermo-électromécanique.

AIM OF THE STUDY: In a healthy heart, the mechanoelectric feedback (MEF) process acts as an intrinsic regulatory mechanism of the myocardium which allows the normal cardiac contraction by damping mechanical perturbations in order to generate a new healthy electromechanical situation. However, under certain conditions, the MEF can be a generator of dramatic arrhythmias by inducing local electrical depolarizations as a result of abnormal cardiac tissue deformations, via stretch-activated channels (SACs). Then, these perturbations can propagate in the whole heart and lead to global cardiac dysfunctions. In the present study, we qualitatively investigate the influence of temperature on autonomous electrical activity generated by the MEF. METHOD: We introduce a one-dimensional time-dependent model containing all the key ingredients that allow accounting for the excitation-contraction coupling, the MEF and the thermoelectric coupling. RESULTS: Our simulations show that an autonomous electrical activity can be induced by cardiac deformations, but only inside a certain temperature interval. In addition, in some cases, the autonomous electrical activity takes place in a periodic way like a pacemaker. We also highlight that some properties of action potentials, generated by the mechanoelectric feedback, are significantly influenced by temperature. Moreover, in the situation where a pacemaker activity occurs, we also show that the period is heavily temperature-dependent. CONCLUSIONS: Our qualitative model shows that the temperature is a significant factor with regards to the electromechanical behavior of the heart and more specifically, with regards to the autonomous electrical activity induced by the cardiac tissue deformations.

Patient specific identification of the cardiac driver function in a cardiovascular system model.

The cardiac muscle activation or driver function, is a major determinant of cardiovascular dynamics, and is often approximated by the ratio of the left ventricle pressure to the left ventricle volume. In an intensive care unit, the left ventricle pressure is usually never measured, and the left ventricle volume is only measured occasionally by echocardiography, so is not available real-time. This paper develops a method for identifying the driver function based on correlates with geometrical features in the aortic pressure waveform. The method is included in an overall cardiovascular modelling approach, and is clinically validated on a porcine model of pulmonary embolism. For validation a comparison is done between the optimized parameters for a baseline model, which uses the direct measurements of the left ventricle pressure and volume, and the optimized parameters from the approximated driver function. The parameters do not significantly change between the two approaches thus showing that the patient specific approach to identifying the driver function is valid, and has potential clinically.

Unique parameter identification for cardiac diagnosis in critical care using minimal data sets.

Lumped parameter approaches for modelling the cardiovascular system typically have many parameters of which a significant percentage are often not identifiable from limited data sets. Hence, significant parts of the model are required to be simulated with little overall effect on the accuracy of data fitting, as well as dramatically increasing the complexity of parameter identification. This separates sub-structures of more complex cardiovascular system models to create uniquely identifiable simplified models that are one to one with the measurements. In addition, a new concept of parameter identification is presented where the changes in the parameters are treated as an actuation force into a feed back control system, and the reference output is taken to be steady state values of measured volume and pressure. The major advantage of the method is that when it converges, it must be at the global minimum so that the solution that best fits the data is always found. By utilizing continuous information from the arterial/pulmonary pressure waveforms and the end-diastolic time, it is shown that potentially, the ventricle volume is not required in the data set, which was a requirement in earlier published work. The simplified models can also act as a bridge to identifying more sophisticated cardiac models, by providing an initial set of patient specific parameters that can reveal trends and interactions in the data over time. The goal is to apply the simplified models to retrospective data on groups of patients to help characterize population trends or un-modelled dynamics within known bounds. These trends can assist in improved prediction of patient responses to cardiac disturbance and therapy intervention with potentially smaller and less invasive data sets. In this way a more complex model that takes into account individual patient variation can be developed, and applied to the improvement of cardiovascular management in critical care.

Model-based identification and diagnosis of a porcine model of induced endotoxic shock with hemofiltration.

A previously validated cardiovascular system (CVS) model and parameter identification method for cardiac and circulatory disease states are extended and further validated in a porcine model (N=6) of induced endotoxic shock with hemofiltration. Errors for the identified model are within 10% when the model is re-simulated and compared to the clinical data. All identified parameter trends over time in the experiments match clinically expected changes both individually and over the cohort. This work represents a further clinical validation of these model-based cardiovascular diagnosis and therapy guidance methods for use with monitoring endotoxic disease states.

Model-based cardiac diagnosis of pulmonary embolism.

A minimal cardiac model has been shown to accurately capture a wide range of cardiovascular system dynamics commonly seen in the intensive care unit (ICU). However, standard parameter identification methods for this model are highly non-linear and non-convex, hindering real-time clinical application. An integral-based identification method that transforms the problem into a linear, convex problem, has been previously developed, but was only applied on continuous simulated data with random noise. This paper extends the method to handle discrete sets of clinical data, unmodelled dynamics, a significantly reduced data set theta requires only the minimum and maximum values of the pressure in the aorta, pulmonary artery and the volumes in the ventricles. The importance of integrals in the formulation for noise reduction is illustrated by demonstrating instability in the identification using simple derivative-based approaches. The cardiovascular system (CVS) model and parameter identification method are then clinically validated on porcine data for pulmonary embolism. Errors for the identified model are within 10% when re-simulated and compared to clinical data. All identified parameter trends match clinically expected changes. This work represents the first clinical validation of these models, methods and approach to cardiovascular diagnosis in critical care.

Confirmation of high cytokine clearance by hemofiltration with a cellulose triacetate membrane with large pores: an in vivo study.

OBJECTIVE: To confirm in vivo the hypothesis that hemofiltration with a large pore membrane can achieve significant cytokine clearance. METHOD: We used a well-known animal model of endotoxinic shock (0.5 mg/kg of lipopolysaccharide from Escherichia Coli over a period of 30 mins). Six pigs were hemofiltrated for 3 hours with a large pore membrane (78 A pore, 80 kDa cut off) (Sureflux FH 70, Nipro, Osaka, Japan). The ultrafiltration rate was 45 ml/kg/min. Samples were taken from arterial, venous line and in the ultrafiltrate at T120 and T240. We measured concentrations of interleukin 6, interleukin 10 and albumin. RESULTS: At T120 and T240, the IL-6 clearances were 22 +/- 7 and 15 +/- 3 ml/min, respectively. The IL-6 sieving coefficients were 0.97 and 0.7 at T120 and T240, respectively. At T120 and T240, the IL-10 clearances were 14 +/- 4 and 10 +/- 7 ml/min, respectively. The sieving coefficients were 0.63 and 0.45 at T120 and T240, respectively. The concentrations of IL-6 and IL-10 were the same at T0 and T240. At T60 and T240, the plasmatic albumin concentrations were 24 +/- 4 g/L and 23 +/- 4 g/L, respectively (p = 0.13). CONCLUSIONS: In this animal model of endotoxinic shock, we confirm the high cytokine clearance observed when hemofiltration is applied to a large pore membrane. The loss of albumin seems negligible. The impact of such clearances on hemodynamic stability and survival remains to be proved.

Amplitude equations for Rayleigh-Bénard convective rolls far from threshold.

An extension of the amplitude method is proposed. An iterative algorithm is developed to build an amplitude equation model that is shown to provide precise quantitative results even far from the linear instability threshold. The method is applied to the study of stationary Rayleigh-Bénard thermoconvective rolls in the nonlinear regime. In particular, the generation of second and third spatial harmonics is analyzed. Comparison with experimental results and direct numerical calculations is also made and a very good agreement is found.

Coupled capillary and gravity-driven instability in a liquid film overlying a porous layer.

In this work, we study the problem of onset of thermal convection in a fluid layer overlying a porous layer, the whole system being heated from below. We use Brinkman's model to describe the porous medium and determine the corresponding linear stability equations. The eigenvalue problem is solved by means of a modified Galerkin method. The behavior of the critical wave number and temperature gradient is discussed in terms of the various parameters of the system. We also emphasize the influence of the boundary conditions at the upper surface of the fluid layer; in particular, we examine the role of a free surface whose surface tension is temperature dependent (Marangoni effect). Comparison with earlier works is also made.